DESCRIPTION: (Applicant's Abstract) The long-term goal of this project is to explore the central mechanisms involved in persistent pain. The lack of understanding of central mechanisms has made persistent pain difficult to treat. Peripheral sensitization (increased sensitivity of primary afferent nociceptors) and central sensitization (enhanced nociceptive transmission in the spinal cord) contribute to persistent pain induced by tissue or nerve injury. However, descending influences from supraspinal structures on spinal sensory transmission during persistent pain haven't been investigated. The present proposal tests the hypothesis that descending biphasic (facilitatory and inhibitory) modulation from the rostromedial medulla (RMM) contribute to persistent pain by enhancing spinal sensory transmission. Single neurons in the RMM will be recorded to examine plastic changes of single neurons in the RMM during persistent pain induced by a subcutaneous injection of formalin into the receptive field. Changes in neuron activity in the RMM may effect spinal sensory transmission through descending biphasic modulation. Thus, responses of spinal neurons to noxious stimuli will be recorded to determine the effects of descending biphasic modulation from the RMM on spinal nociceptive transmission during persistent pain. In addition, responses of spinal neurons to non-noxious stimuli will be measured to test the effects of descending biphasic modulation from the RMM on spinal non-nociceptive transmission during persistent pain. Behavioral and pharmacological experiments will be carried out to characterize the effects of descending biphasic modulation on behavioral reflexes and spinal receptor(s) which mediate the effects during persistent pain. Electrophysiological, behavioral and pharmacological approaches will generate converging information about the role of descending influences on spinal plasticity before and during persistent noxious input. It is hypothesized that the RMM plays an important role in the induction and maintenance of spinal changes associated with persistent pain.